Abstract
The present experiment was carried out to explore the effect of endogenous androgen on rat prostate carcinogenesis induced by 3,2′‐dimethyl‐4‐aminobiphenyl (DMAB) and testosterone propionate (TP) or 5α‐dihydrotestosterone (DHT) with or without ethinyl estradiol (EE). In order to eliminate the influence of endogenous androgen, F344 rats were orchiectomized just after initiation with the prostate carcinogen, DMAB, and then given TP, DHT, TP plus EE or DHT plus EE for 40 weeks. The results demonstrated that while administration of TP following DMAB treatment causes invasive carcinomas in the lateral and anterior prostate and seminal vesicles, DHT does not exhibit equivalent effects. Synergistic enhancement was also evident with TP plus EE, but not with DHT plus EE. The incidences of prostatic and seminal vesicle lesions in all groups of the present experiment, except for the group given castration without hormonal supplement, were equivalent to those previously found in non‐castrated animals. Therefore, the present findings indicate that endogenous testosterone may not be required for promotion hy TP/EE of DMAB‐initiated prostate carcinogenesis and that it may not contribute to the actions of DHT.
Keywords: Prostate carcinogenesis; Androgen; Ethinyl estradiol; 3,2′‐Dimethyl‐4‐amino‐biphenyl; Castration
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REFERENCES
- 1. ) Noble , R. L.The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration . Cancer Res. , 37 , 1929 – 1933 ( 1977. ). [PubMed] [Google Scholar]
- 2. ) Noble , R. L.Production in the Noble rat of carcinoma of the dorsal prostate and response of estrogen‐dependent transplants to sex hormones and tamoxifen . Cancer Res. , 40 , 3547 – 3550 ( 1980. ). [PubMed] [Google Scholar]
- 3. ) Drago , J. R.The induction of Noble rat prostatic carcinomas . Anticancer Res. , 4 , 255 – 256 ( 1984. ). [PubMed] [Google Scholar]
- 4. ) Pollard , M. , Luckert , P. H. and Schmidt , M. A.Induction of adenocarcinomas in Lobund‐Wistar rats by testosterone . Prostate , 3 , 563 – 568 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Pour , P. M. and Stepan , K.Induction of prostatic carcinomas and lower urinary tract neoplasms by combined treatment of intact and castrated rats with testosterone propionate and N‐nitrosobis(2‐oxopropyl)amine . Cancer Res. , 47 , 5699 – 5709 ( 1987. ). [PubMed] [Google Scholar]
- 6. ) Pollard , M. , Snyder , D. L. and Luckert , P. H.Dihydrotestosterone does not induce prostate adenocarcinoma in L‐W rats . Prostate , 10 , 325 – 331 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Shirai , T. , Imaida , K. , Masui , T. , Iwasaki , S. , Mori , T. , Kato , T. and Ito , N.Effects of testosterone, and estrogen on 3,2′‐dimethyl‐4‐aminobiphenyl‐induced rat prostate carcinogenesis . Int. J. Cancer , 57 , 224 – 228 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Bosland , M. C. , Ford , H. and Horton , L.Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague‐Dawley Hsd:SD rats treated with a combination of testosterone and estradiol‐17β or diethylstilbestrol . Carcinogenesis , 16 , 1311 – 1318 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Shirai , T. , Fukushima , S. , Ikawa , E. , Tagawa , Y. and Ito , N.Induction of prostate carcinoma in situ at high incidence in F344 rats by a combination of 3,2′‐dimethyl‐4‐aminobiphenyl and ethinylestradiol . Cancer Res. , 46 , 6423 – 6426 ( 1986. ). [PubMed] [Google Scholar]
- 10. ) Shirai , T. , Nakamura , A. , Fukushima , S. , Tada , M. , Morita , T. and Ito , N.Immunohistochemical demonstration of carcinogen‐DNA adducts in target and non‐target tissues of rats given a prostate carcinogen, 3,2′‐dimethyl‐4‐aminobiphenyl . Carcinogenesis , 11 , 653 – 658 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Shirai , T. , Tamano , S. , Sano , M. , Imaida , K. , Hagiwara , A. , Futakuchi , M. , Takahashi , S. and Hirose , M.Site‐specific effects of testosterone propionate on the prostate of rat pretreated with 3,2′‐dimethyl‐4‐aminobiphenyl; dose‐dependent induction of invasive carcinomas . Jpn. J. Cancer Res. , 86 , 645 – 648 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. ) Shirai , T. , Tamano , S. , Kato , T. , Iwasaki , S. , Takahashi , S. and Ito , N.Induction of invasive carcinomas in the accessory sex organs other than the ventral prostate of rats given 3,2′‐dimethyl‐4‐aminobiphenyl and testosterone propionate . Cancer Res. , 51 , 1264 – 1269 ( 1991. ). [PubMed] [Google Scholar]
- 13. ) Syms , A. J. , Norris , J. S. and Smith , R. G.Proliferation of a highly androgen‐sensitive ductus deferens cell line (DDT1MF‐2) is regulated by glucocorticoids and modulated by growth on collagen . In Vitro , 19 , 929 – 936 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Walsh , P. C. and Wilson , J. D.The induction of prostatic hypertrophy in the dog with androstanediol . J. Clin. Invest. , 57 , 1093 – 1098 ( 1976. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. ) Moore , R. J. , Gazak , J. M. and Wilson , J. D.Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17β‐ estradiol . J. Clin. Invest. , 63 , 351 – 357 ( 1979. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. ) Mobbs , B. G. , Johnson , I. E. , Connolly , J. G. and Thompson , J.Concentration and cellular distribution of androgen receptor in human prostatic neoplasia: can estrogen treatment increase androgen receptor content ? J. Steroid Biochem. , 19 , 1279 – 1290 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Miyata , E. , Kawabe , M. , Sano , M. , Takesada , N. , Takahashi , S. and Shirai , T.The effects of tamoxifen, an antiestrogen, on rat prostate carcinogenesis by 3,2′‐dimethyl‐4‐aminobiphenyl and testosterone do not support an estrogen role in testosterone promotion . Prostate , ( 1996. ). in press . [DOI] [PubMed] [Google Scholar]